STIM is a Ca2+ sensor essential for Ca2+-store- depletion-triggered Ca2+ influx

Jen Liou, Man Lyang Kim, Do Heo Won, Joshua T. Jones, Jason W. Myers, James E. Ferrell, Tobias Meyer

Research output: Contribution to journalArticle

1456 Citations (Scopus)

Abstract

Ca2+ signaling in nonexcitable cells is typically initiated by receptor-triggered production of inositol-1,4,5-trisphosphate and the release of Ca2+ from intracellular stores [1]. An elusive signaling process senses the Ca2+ store depletion and triggers the opening of plasma membrane Ca2+ channels [2-5]. The resulting sustained Ca2+ signals are required for many physiological responses, such as T cell activation and differentiation [6]. Here, we monitored receptor-triggered Ca2+ signals in cells transfected with siRNAs against 2,304 human signaling proteins, and we identified two proteins required for Ca 2+-store-depletion-mediated Ca2+ influx, STIM1 and STIM2 [7-9]. These proteins have a single transmembrane region with a putative Ca 2+ binding domain in the lumen of the endoplasmic reticulum. Ca 2+ store depletion led to a rapid translocation of STIM1 into puncta that accumulated near the plasma membrane. Introducing a point mutation in the STIM1 Ca2+ binding domain resulted in prelocalization of the protein in puncta, and this mutant failed to respond to store depletion. Our study suggests that STIM proteins function as Ca2+ store sensors in the signaling pathway connecting Ca2+ store depletion to Ca2+ influx.

Original languageEnglish (US)
Pages (from-to)1235-1241
Number of pages7
JournalCurrent Biology
Volume15
Issue number13
DOIs
StatePublished - Jul 12 2005

Fingerprint

calcium
Sensors
Cell membranes
Proteins
Cell Membrane
Inositol 1,4,5-Trisphosphate
T-cells
Ion Channels
Point Mutation
Endoplasmic Reticulum
proteins
Cell Differentiation
Chemical activation
plasma membrane
T-Lymphocytes
receptors
point mutation
physiological response
endoplasmic reticulum
T-lymphocytes

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)

Cite this

Liou, J., Kim, M. L., Won, D. H., Jones, J. T., Myers, J. W., Ferrell, J. E., & Meyer, T. (2005). STIM is a Ca2+ sensor essential for Ca2+-store- depletion-triggered Ca2+ influx. Current Biology, 15(13), 1235-1241. https://doi.org/10.1016/j.cub.2005.05.055

STIM is a Ca2+ sensor essential for Ca2+-store- depletion-triggered Ca2+ influx. / Liou, Jen; Kim, Man Lyang; Won, Do Heo; Jones, Joshua T.; Myers, Jason W.; Ferrell, James E.; Meyer, Tobias.

In: Current Biology, Vol. 15, No. 13, 12.07.2005, p. 1235-1241.

Research output: Contribution to journalArticle

Liou, J, Kim, ML, Won, DH, Jones, JT, Myers, JW, Ferrell, JE & Meyer, T 2005, 'STIM is a Ca2+ sensor essential for Ca2+-store- depletion-triggered Ca2+ influx', Current Biology, vol. 15, no. 13, pp. 1235-1241. https://doi.org/10.1016/j.cub.2005.05.055
Liou, Jen ; Kim, Man Lyang ; Won, Do Heo ; Jones, Joshua T. ; Myers, Jason W. ; Ferrell, James E. ; Meyer, Tobias. / STIM is a Ca2+ sensor essential for Ca2+-store- depletion-triggered Ca2+ influx. In: Current Biology. 2005 ; Vol. 15, No. 13. pp. 1235-1241.
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